Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China.
PLoS One. 2024 Apr 30;19(4):e0302650. doi: 10.1371/journal.pone.0302650. eCollection 2024.
Zhilong Huoxue Tongyu Capsule (ZL) is a Chinese medicine used for the treatment of cardio-cerebral diseases. However, the pharmacological mechanisms underlying its regulation of myocardial ischemia/reperfusion injury (MI/RI) remain unclear.
This study aims to investigate the effects and mechanisms of ZL on MI/RI in mice.
C57BL/6J mice were randomly assigned to four groups: Sham group, I/R group, ZL group, and ZLY group. The MI/RI mouse model was established by ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 120 minutes to restore blood perfusion. Cardiac function was evaluated using cardiac ultrasound. Histopathological changes and myocardial infarction area were assessed using Hematoxylin and eosin (H&E) staining and triphenyltetrazolium chloride (TTC) staining. The changes in oxidative stress- and ferroptosis-related markers were detected. RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of ZL in improving MI/RI.
Our findings demonstrated that ZL exerted a protective effect against MI/RI by inhibiting ferroptosis, evidenced by the upregulation of antioxidant enzymes such as GSH and GPX4, coupled with the downregulation of ACSL4, a pro-ferroptosis factor. Furthermore, ZL positively impacted the PI3K/AKT/Nrf2 pathway by promoting ATPase activities and enhancing the relative protein expression of its components. Notably, the administration of a PI3K/AKT inhibitor reversed the antioxidant and anti-ferroptosis effects of ZL to some extent, suggesting a potential role for this pathway in mediating ZL's protective effects.
ZL protects against MI/RI-induced ferroptosis by modulating the PI3K/AKT signaling pathway, leading to increased Nrf2 expression and activation of the HO-1/GPX4 pathway. These findings shed light on the potential therapeutic mechanisms of ZL in the context of cardiovascular diseases.
蛭龙活血通瘀胶囊（ZL）是一种用于治疗心脑血管疾病的中药。然而，其调节心肌缺血/再灌注损伤（MI/RI）的药理机制尚不清楚。
本研究旨在探讨 ZL 对 MI/RI 小鼠的作用及机制。
C57BL/6J 小鼠随机分为四组：假手术组、I/R 组、ZL 组和 ZLY 组。通过结扎左前降支冠状动脉 30 分钟，再灌注 120 分钟恢复血流来建立 MI/RI 小鼠模型。使用心脏超声评估心功能。通过苏木精和伊红（H&E）染色和三苯基四唑氯（TTC）染色评估心肌组织病理学变化和心肌梗死面积。检测氧化应激和铁死亡相关标志物的变化。通过 RT-qPCR、Western blot 和 ELISA 进一步探讨 ZL 改善 MI/RI 的作用机制。
我们的研究结果表明，ZL 通过抑制铁死亡对 MI/RI 发挥保护作用，证据是抗氧化酶如 GSH 和 GPX4 的上调，同时伴随着促铁死亡因子 ACSL4 的下调。此外，ZL 通过促进 ATPase 活性和增强其组成成分的相对蛋白表达，对 PI3K/AKT/Nrf2 通路产生积极影响。值得注意的是，PI3K/AKT 抑制剂的给药在一定程度上逆转了 ZL 的抗氧化和抗铁死亡作用，表明该通路在介导 ZL 的保护作用中可能发挥作用。
ZL 通过调节 PI3K/AKT 信号通路，抑制 MI/RI 诱导的铁死亡，从而增加 Nrf2 表达和激活 HO-1/GPX4 通路，保护心肌免受损伤。这些发现为 ZL 在心血管疾病中的潜在治疗机制提供了线索。
